Delivery devices and their use

ABSTRACT

A device for actively releasing material(s) (e.g. intra ruminally) having a plurality of dispensing reservoirs. Each electrolytic cell is capable upon energization under the control of a microprocessor after initiation of generating a gas which will cause (e.g. through action on a piston) by displacement of the material(s) of its respective reservoir sufficient displacement of or change to closure means of that reservoir thereby to allow release of the material(s).

TECHNICAL FIELD

The present invention relates to improvements in and/or relating todelivery devices and their use.

Delivery devices such as those utilised to deliver medicaments,supplements and/or other agents into a body cavity (eg; vagina, rumen,etc). Delivery of substances into the rumen of a ruminant whilst adelivery device is retained in the rumen is well known.

BACKGROUND OF THE INVENTION

Generally such intra ruminal devices take the form of a device or boluscapable ofbeing inserted into the rumen by an appropriate applicator tobe retained over at least the delivery period by either

(a) retention means of variable geometry, e.g. deployable wings or thelike, or

(b) retention means reliant upon density.

Known for ruminal delivery are devices capable of providing either acontinuous (even if not strictly constant) or a pulsed delivery. In thelater category are such devices as those reliant upon galvanic action toprovide periodic exposure to a fresh reservoir of the dry or fluidcomposition of or containing the agent to be released.

Agents to be delivered into a ruminant intra ruminally are well known.Their function ranges from that of providing protection against bloat,agents to render more efficient the uptake of food, agents adapted todeal with mineral or vitamin deficiencies, agents to deal with attacksby pests (whether internal or external, etc).

The present invention relates to an active device which does not relyupon the environmental conditions of the device within the rumen of ananimal once administered and which is active in a controlled way in itsrelease profile.

Devices of this type are known. For example, in U.S. Pat. No. 4564363 ofSmith Kline Beecham Corporation (the full content of which is herebyhere included by way of reference) there is disclosed a multi reservoirbolus type device providing for a delayed release of the contents of atleast one reservoir under the control of an electrically detonatablesquib.

The present invention relates to a device of this kind having aplurality of separately controllable dischargeable reservoirs in adevice which is either a density or variable geometry type retentiondevice for intra ruminal insertion.

It is an object of the present invention to provide a viable body cavitydelivery device (eg; intra ruminal bolus or device) capable of timedrelease of multiple reservoirs of agent to be released (whether the sameor different) and irrespective of whether or not such quantities to bereleased at different times are the same or different or are todelivered at different rates or in different quantities. An alternativeobject is to at least provide the public with a useful choice in respectof active release devices for body cavity (eg; the rumen) insertion. Astill other object is to provide a squibless active delivery system.

BRIEF SUMMARY OF THE INVENTION

Accordingly in a first aspect the present invention consists in a devicefor actively releasing material(s) intra ruminally comprising orincluding

a housing having a plurality of reservoirs each having an outlet fromsaid housing,

material(s) to be released in each of said reservoirs,

closure means for at least some of said outlets to protect thematerial(s) from passive release,

an electrolytic cell for each of said reservoirs having closure means,each electrolytic cell being capable when activated of generating a gaswhich will cause by displacement of the material(s) of its respectivereservoir sufficient displacement of or change to the closure means ofthat reservoir thereby to allow release of the material(s), and

means to activate selectively each electrolytic cell.

Preferably the device is an intra ruminal device.

Preferably said electrolytic cell of each reservoir is capable throughthe generation of the gas of expressing at least some of the material(s)out of the outlet of the reservoir.

Preferably the gas of at least some reservoir acts indirectly on thematerial(s).

Preferably the gas of at least one reservoir acts of materialdisplacement means selected from

(i) a piston or plunger arrangement, and

(ii) a collapsible bladder or deformable membrane type arrangement.

Preferably said means to activate selectively each electrolytic cellincludes a timer and/or logic means capable of delaying the activationof at least one of the electrolytic cells to thus delay the activerelease of the materials.

Preferably at least one of said closure means is a cap or theequivalent.

Preferably at least one of said closure means is tethered to saidhousing.

Preferably a film or foil material, or laminate thereof, provides, atleast in part, a closure means for at least one of said reservoirs.

Preferably said film or foil is rupturable to allow the active releaseof the material(s) of the respective reservoir.

Preferably said electrolytic cell of at least one of said reservoirs iscapable of being activated so as to provide a timed release of thematerials within the respective reservoir.

Preferably said battery is capable of powering the electrolytic cells.

Preferably a switch is provided to energise the device whereupon, at anappropriate time or times, at the control of said means to activate eachelectrolytic cell, there is an appropriate energising of a particularelectrolytic cell and thereafter the active release of the material(s)of the particular reservoir.

Accordingly in another aspect the present invention may broadly be saidto consist in an intra ruminal device consisting of, comprising orincluding

a housing having a plurality of reservoirs each having an outlet fromsaid housing,

closure means for at least some of said outlets,

material(s) to be released from each reservoir in each of saidreservoirs,

material displacement means to reduce the volume of each such reservoir,such material displacement means being selected from

(i) a piston or plunger arrangement, and

(ii) a collapsible bladder or deformable membrane type arrangement,

electrolytic cells, each dedicated to one of said reservoirs, and eachpositioned to generate, when activated, a gas which by action on saidmaterial displacement means will cause the closure means of itsreservoir to allow access of the material(s) (in use) to ruminalfluids(s) and/or membrane(s), and

means to activate selectively each electrolytic cell.

Preferably said means to activate selectively each electrolytic cellincludes a timer and/or logic means capable of delaying the activationof at least one and preferably several of the electrolytic cells to thusdelay the active release of the materials into the rumen (in use) of therespective reservoirs.

Preferably a piston or plunger arrangement is provided in each reservoirand each reservoir is in the form of a barrel of any appropriate crosssection for the piston or plunger. Preferably however the cross sectionis circular.

Preferably the closure means is rupturable or sufficiently movable ordeformable at said outlets by the material or materials of theparticular reservoir under the action of gas on its materialdisplacement means to achieve the release effect of the hitherto atleast substantially sealed material(s).

Preferably said device includes as part of said means to activate abattery capable of powering the electrolytic cells.

Preferably a switch is provided to energise the device whereupon at anappropriate time or times, at the control of said means to activate eachelectrolytic cell, there is an appropriate energising of a particularelectrolytic cell and thereafter the active release of the material(s)of the particular reservoir.

Preferably the arrangement involves the provision of at least onereservoir which substantially immediately makes its materials available(irrespective of whether or not its reservoir requires closure means tobe dislodged, ruptured or otherwise affected and irrespective of whetheror not there is any active release from such a reservoir under theaction of a said material displacement means).

Preferably rumen retention has

(i) a density which will result in rumen retention,

(ii) a variable geometry retention configuration, or

(iii) or both (i) and (ii).

In yet a further aspect the present invention consists in an intraruminal device consisting of, comprising or including

means (for example, a housing) defining a reservoir having an outlet,said reservoir being of a kind which will allow the movement of plungersor pistons towards and out of said outlet,

a plurality of separate plungers or pistons positioned at differentposition from said outlet,

material(s) to be released interposed between each of said plungers orpistons within parts of said reservoir,

an electrolytic cell capable of generating a gas when activated to causemovement of the assemblage of materials and plungers or pistons to saidoutlet, and

means to activate said electrolytic cell,

the construction and arrangement being such that after intra ruminalinsertion of the device, the means to activate said electrolytic cellcan present serially the different masses of the materials within thereservoir to or into the rumen, a plunger or piston being dischargedfrom the outlet prior to presenting for release the next mass ofmaterial to be serially presented.

Preferably said means to activate is of a kind previously described.

Preferably the arrangement is substantially as hereinafter described.

Preferably said device (in any of its forms) is of a variable geometryretention kind.

Preferably said means to activate each or the electrolytic cell canlikewise activate a release mechanism for the variable geometry means sothat the device after such activation (which is after the release of atleast substantially all of the materials desired) can be discharged fromthe rumen by the ruminant into whom it has been inserted.

Preferably said variable geometry means is affected by a squib.

In still other variants a weighting device can be disassociated underthe action of such means to activate so as to render parts of theoriginal device thereafter dischargeable from the rumen under the actionof the ruminant.

In a further aspect the present invention consists in insitu, in therumen of a ruminant, a device as previously defined.

In still a further aspect the present invention consists in a method ofdelivering a substance into the rumen of an animal which compriseslocating a device in accordance with the present invention in the rumenof the ruminant, the device having been initiated (for example byactivation of a switch or otherwise) so that a sequence ofmaterial/substance release thereafter results.

In a further aspect the present invention consists in the use intraruminally of a device in accordance with the present invention.

Preferred forms of the present invention will now be described withreference to the accompanying drawings in which;

FIG. 1 shows a device for the time delivery of an active agent, thedevice being of a density type retention device and having multiplebarrels (preferably circular) with the material to be released from eachbarrel being protected by a seal [e.g. of a foil or other material,(e.g. a suitable wax)],

FIG. 2A shows a variable geometry version of the device, the devicehaving means providing retention wings which for the purpose ofinsertion would be configured as is known in the art but which deployafter ruminal insertion, the device having provision for separating thewings from the remainder of the device to thus allow its expulsion by ananimal from its rumen,

FIG. 2B is a view A—A of FIG. 2A,

FIG. 3 is still a further variant of a device in accordance with thepresent invention (this time shown as a density type device but again,as with the device of FIG. 1, being one to which, if desired, variablegeometry means could be attached),

FIG. 4 shows a release profile according to some predetermined programfor devices such as depicted in FIGS. 1 through 3 showing a delay onfirst activation and a periodic release of at least two subsequentreservoirs/barrels,

FIG. 5 is a diagrammatic side elevation of a plunger provided series ofreservoirs some of which are sealed by closure means in the form of abung and one of which is sealed solely by a film or foil or laminationthereof,

FIG. 6 is a top view of an arrangement as shown in FIG. 5 showing how,if desired, at least one bung can be tethered to the housing whichdefines the multiple reservoirs,

FIG. 7 is a similar view to that of FIG. 6 but showing how frangibleregions can be provided to allow selective rupture,

FIG. 8 is a diagram showing a preferred circuit, and

FIG. 9 shows an enlarged layout as might used utilised for a circuit asshown in FIG. 8.

DETAILED DESCRIPTION

In accordance with the present invention reference is made to U.S. Pat.No. 5,527,288 and 5,318,557 of Elan Medical Technologies Limited whichshow the utilisation of an electrolytic cell capable of generating gasunder an electric current.

Reference is also made to U.S. Pat. No. 5,354,264 of Insutech Inc whichdiscloses a drug delivery device which utilises gas pressure from freeoxygen and hydrogen derived from the electrolysis of water at theelectrodes in negatively charged polymeric hydrogels by electro-osmosis.In U.S. Pat. No. 5,354,264 there is described the use of that gaspressure to force the infusion of drugs through appropriate means intothe body.

The present invention recognises a desire to provide periodicavailability of stored materials in a rumen retainable device and tomake different quantities of the material available at different timesfor assimilation by the animal into which the device has been inserted.

FIGS. 1 and 2 (i.e. 2 a and 2B) show devices of same type, i.e.individual barrels from which the materials to be discharged can beselectively released.

Referring to FIG. 1 there is shown for each barrel or reservoir aretained quantity of substance or material 1 to be released and anoutlet at 2 which is sealed by a rupturable foil 3. Other forms ofclosure means can be utilised, for example, wax or a plug. Indeed FIG. 2shows plug like members 4 which can, if desired, be an appropriate wax.

Within each of the barrels is shown a plunger or piston 5. Positioned inor communicable with each barrel behind the plunger 5 in the barrel ineach instance is the electrolytic cell 6 with its electrodes.

Each electrolytic cell is connected to activating means which includesan electronic control unit 7, a battery 8 and a switch 9.

The version shown in FIG. 2 is provided with wings 10 capable under thecontrol of the electronic control unit 7 of activating a squib or othermeans 11 (it could even be a similar electrolytic cell) to discharge thedeformable variable geometry wing defining member 10 from the remainderof the device to thus allow expulsion of the residual components fromthe rumen. Not shown is the density version which may likewise dischargea weight using a similar mechanism.

The release profile envisaged with such a device is along the linesshown in FIG. 4.

FIG. 3 shows a different variant of the present invention where there isa single barrel having separated quantities in the barrel of thematerial 1 to be released. In this form a series of interposing plungersor pistons 4 are provided to interpose between the separate quantitiesand preferably also a seal 12.

In this form of the present invention a single large electrolytic cell 6is utilised but is activated selectively so as in series and overselected time periods (i.e. by the generation of still more gas to addto that already generated and still trapped) to dislodge that member 5in advance of the next quantity of materials to be released 1. A profileagain of the kind envisaged in FIG. 4 is achievable.

FIG. 5 shows a side view of a preferred form of device having, by way ofexample, four reservoirs. Three are provided with a bung or the likepreferably overlaid by a sheet of rupturable material, one of thedevices is shown without a bung as that preferably as the first todischarge its material upon insertion.

In each instance as shown in FIG. 5 a piston is provided to cause thedischarge of the contents.

FIG. 6 shows a top view of a device such as that shown in FIG. 5 showinghow if desired one or more of the bungs can be tethered to the top ofthe housing.

FIG. 7 shows how a rupturable laminate may overlie the arrangement of,for example, FIG. 6.

In use therefore an aluminium foil of a configuration such as FIG. 7 maybe laminated over the openings to the reservoirs and marked in such amanner that rupture occurs by the action of the reservoir contents beingexpelled. This is irrespective of whether or not any bungs are usedinstead of or under the rupturable laminate.

The contents of the reservoirs may be expelled under the influence of anelectronic microprocessor and feedback mechanism. Sensors external tothe device may upon the detection of a predetermined marker activateelectrolysis and expel the content of the reservoir.

Further feedback mechanism may act to terminate, decrease the rate,increase the rate or extend electrolysis upon determining a particularparameter value, for example,

Parameter Response reservoir has not released contents increase rate orduration of after appropriate time has passed electrolysis sufficientelectrolysis has occurred to terminate or decrease rate of openreservoir closer electrolysis metabolite or biological marker detectedinitiate electrolysis to expel contents of reservoir metabolite orbiological marker detected terminate electrolysis to retain contents ofreservoir

FIG. 8 shows a preferred circuit for a transistor and resistor housed ina single SOT-23 package (DTC114T “Digital Transistor”—Farnell 662-781).

The circuit utilises a PIC16C54A—04/SO Microprocessor to provide thecontrol mechanism for the hydrogel cells.

Specifically it is used to generate the activation sequence, timing andthe rate of gas production in each cell.

Two 3V batteries provide the power source for the circuit.

The microprocessor is powered from one 3V battery.

Each output switches 6V to the e-gel cell via a digital transistorDTC114T (base resistor and transistor in same package).

An LED is used to provide visual indication of the circuit's operation.

The circuit uses a 32.768 kHz crystal oscillator. The timing delays aregenerated from this clock source.

An external resistor may be used to limit the current flowing to thehydrogel cell and thereby limit the rate of gas production.

When the circuit is powered up (from an external switch) the LED flashes10 times to indicate that the circuit is active.

After a programmed delay one (or more) of the outputs is switched on fora programmed time, after which the output may be turned off.

Each output consists of six transistors, switching 6V to the hydrogelcells. Each e-gel cell may be connected to more than one transistoroutput.

Each time an output is switched on, the LED will flash a programmednumber of times to indicate that an output circuit has been activated.

At the end of the routine, the microprocessor loops (ie; does nothing)until its battery is exhausted.

The program may be modified to suit a specific number of outputs (e-gelcells) or required timing delays.

FIG. 9 shows one suitable microprocessor board arrangement for such adevice (enlarged 2:1).

It is believed that devices in accordance with the present inventionwill find widespread acceptance.

What is claimed is:
 1. A device for actively releasing material(s)comprising or including a housing having a plurality of reservoirs eachhaving an outlet from said housing, material(s) to be released in eachof said reservoirs, closure means for at least some of said outlets toprotect the material(s) from passive release, an electrolytic cell foreach of said reservoirs having closure means, each electrolytic cellbeing capable when activated of generating a gas which will cause bydisplacement of the material(s) of its respective reservoir sufficientdisplacement of or change to the closure means of that reservoir therebyto allow release of the material(s), and means to activate selectivelyeach electrolytic cell.
 2. A device as claimed in claim 1 wherein saidelectrolytic cell of each reservoir is capable through the generation ofthe gas of expressing at least some of the material(s) out of the outletof the reservoir.
 3. A device as claimed in claim 1 wherein the gas ofat least some reservoir acts indirectly on the material(s).
 4. A deviceas claimed in claim 3 wherein the gas of at least one reservoir acts ofmaterial displacement means selected from (i) a piston or plungerarrangement, and (ii) a collapsible bladder or deformable membrane typearrangement.
 5. A device as claimed in claim 1 wherein said means toactivate selectively each electrolytic cell includes a timer and/orlogic means capable of delaying the activation of at least one of theelectrolytic cells to thus delay the active release of the materials. 6.A device as claimed in claim 1 wherein at least one of said closuremeans is a cap or the equivalent.
 7. A device as claimed in claim 6wherein at least one of said closure means is tethered to said housing.8. A device as claimed in claim 1 wherein a film or foil material, orlaminate thereof, provides, at least in part, a closure means for atleast one of said reservoirs.
 9. A device as claimed in claim 8 whereinsaid film or foil is rupturable to allow the active release of thematerial(s) of the respective reservoir.
 10. A device as claimed inclaim 1 wherein said electrolytic cell of at least one of saidreservoirs is capable of being activated so as to provide a timedrelease of the materials within the respective reservoir.
 11. A deviceas claimed in claim 1 which includes a battery capable of powering theelectrolytic cells.
 12. A device as claimed in claim 1 wherein a switchis provided to energise the device whereupon, at an appropriate time ortimes, at the control of said means to activate each electrolytic cell,there is an appropriate energising of a particular electrolytic cell andthereafter the active release of the material(s) of the particularreservoir.
 13. A device of claim 1 wherein the device for rumenretention has (i) a density which will result in rumen retention; (ii) avariable geometry retention configuration, or (iii) or both (i) and(ii).
 14. A device of claim 1 for intra ruminal use.
 15. The use intraruminally of a device of claim
 1. 16. A method of delivering a substancein to a body cavity of an animal which comprises locating a device asclaimed in claim 1 in the body cavity, the device having been initiatedso that a sequence of material/substance release thereafter results. 17.A method of claim 16 wherein the body cavity is the rumen of a ruminant.18. An intra ruminal device comprising or including means definingmultiple reservoirs each having an outlet, each said reservoir being ofa kind which will allow the movement of plungers or pistons towards theoutlet of said reservoir, a plunger or piston positioned in each saidreservoir, material(s) to be released interposed between each of saidplungers or pistons and the outlet of its reservoir, an electrolyticcell for each reservoir, each cell being capable of generating a gaswhen activated to cause by action on its plunger or piston movement ofthe assemblage of material(s) out of said outlet, and means toselectively activate each said electrolytic cell, the construction andarrangement being such that after intra ruminal insertion of the device,the means to selectively activate each said electrolytic cell canpresent serially the different masses of the material(s) within thereservoirs to or into the rumen.